Objective: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disorder characterized by debilitating fatigue accompanied by pain and impairments in memory, cognition, and concentration. Acetylcholine (ACh) has a plethora of roles in neuronal and neuromuscular transmission.

There are two types of ACh receptors, muscarinic and nicotinic, comprising 17 different subunits of the nicotinic ACh receptor (nAChR) and five different subtypes of the muscarinic receptor (mAChR) that have been identified in humans.

The purpose of this study was to determine the role of ACh receptor (nAChRs and mAChRs) single nucleotide polymorphisms (SNPs) in CFS/ME patients.

One can hope so @Kati. Much of the technological revolution we see now came because computer technology invaded all the labs and homes in the 80s. What we really need though is well funded follow up studies. As always both funding and replication are likely to be an issue.

Severely affected PWME can report respiratory muscle breathing weakness (even from speaking, but without asthma), yet without the 'eye' sign of Myasthenia Gravis or other features. MG patients, like ME sufferers, also get worse as the day goes on, e.g. they run out of muscle energy to the extent they get very distressing symptoms.

So that people can check their results, these are the 17 significant SNPs in the order given in the Abstract with the risk allele in parentheses; my 23andMe results are to the right (I was tested on the prior "v3" platform).

(See Table 1 of the study for ranked order of significance based on p-value.)

It looks like they failed to correct for making hundreds of comparisons. Not too surprising, since their other recent SNP paper did the same thing, if I recall correctly. And it's still Fukuda patients, with no PEM mentioned. Some of the results with the lowest P values might be statistically significant, but if corrections were applied, their chosen P value of 0.05 would probably be far too high.

@Hutan, yes, I think you're right. I didn't read the table correctly. It looks like A1 is always the minor allele, and A2 is always the major, but the risk allele isn't always the minor allele, which isn't unusual, of course. I'll go back and edit my post in the next hour or two.

@Hutan, I take it that you and your son were tested with 23andMe's more recent "v4" test version - since you're missing 2 of the 6 SNPs (out of 17) that I gave results for in post #8 above...?

Also, is the additional SNP you gave, rs1594513, the only other SNP of the 23 given in Table 1 of the full paper that you have results for?

I have that one and also one additional remaining one (rs2175886) from Table 1 that was tested on 23andMe's earlier v3 test version. Here are my results for the two:

rs2175886 (C) CT +/-
rs1594513 (A)* CC -/-

*Risk allele = major allele

So if I understand correctly, people tested on 23andMe's current test version will have results for 4 of the 17 significant SNPs found in the study, plus 1 additional one from Table 1, for a total of 5 SNPs.

People tested on 23andMe's prior version should have 6 of 17, plus 2 additional ones, for a total of 8.

It looks like they failed to correct for making hundreds of comparisons. Not too surprising, since their other recent SNP paper did the same thing, if I recall correctly. And it's still Fukuda patients, with no PEM mentioned. Some of the results with the lowest P values might be statistically significant, but if corrections were applied, their chosen P value of 0.05 would probably be far too high.

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At least with respect to the statistics issue, the results should be okay based on @Mark's reporting here:

Professor Sonya Marshall-Gradisnik + Dr Don Staines:
Presented the results from their recent papers on SNPs in ME/CFS patients. Discussed some of the potential implications of the SNPs they found, and explained why those SNPs look like they fit well with known ME/CFS symptomology. In answer to my question, Marshall-Gradisnik claimed that they had applied statistical corrections to allow for the large number of SNPs they had evaluated, and had employed 'Australia's best biostatistician' to do so.

At least with respect to the statistics issue, the results should be okay based on @Mark's reporting here:

(Bold is Mark's.)

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I intend to seek clarification from the researchers on the statistical details of the error correction in these papers, because based on conversations at IIME and here it's clear that there are quite a few people who are bemused as to how this error-correction can have taken place as claimed. I think we need to see the full workings to get to the bottom of this one. An important question because these findings could be an important part of the jigsaw, if they are replicable.

I intend to seek clarification from the researchers on the statistical details of the error correction in these papers, because based on conversations at IIME and here it's clear that there are quite a few people who are bemused as to how this error-correction can have taken place as claimed. I think we need to see the full workings to get to the bottom of this one. An important question because these findings could be an important part of the jigsaw, if they are replicable.

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Ever find any clarification there? I'd like to cite this study with confidence, if possible.

Ever find any clarification there? I'd like to cite this study with confidence, if possible.

-J

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No, I got side-tracked and never managed to follow up on this; similarly I never managed to write up the rest of my planned series of articles on the IiME conference. I did ask a question about this at IiME conference last year, and the response was (roughly) that Australia's foremost statistician had confirmed the statistical analysis. However, the details of the error-correction calculation remain unclear, it seems. I think it would be a really good idea for someone to follow up on this; @Simon would have the details about what still needs to be clarified. I find your attention to detail, in requiring clarification before citing this study with confidence, to be highly commendable.